Summary: In a joint meeting (1996) organized by the Institute of Medicine and US National Academy of Sciences on Vaccine Associated Adverse Reactions, it was recommended that new strategies must be developed for live viral vaccines so as to reduce the incidence of adverse reactions associated with live, attenuated viral vaccines. Most common complications associated with rubella virus (RV) vaccine occur in adult women and are manifested in polyarthraliga and arthritis, possibly due to persistence and localized viral replication. In addition, in utero fetal infection by RV in the first trimester of pregnancy can cause fetal teratogenesis. Based on the guidelines developed after 1996 meeting, in case of RV, there is a need for elucidating the mechanisms of adverse reactions associated with the vaccine as well as basic understanding of how the virus induces teratogenesis. In the past, we have shown: a) cause of adverse reactions with live virus vaccine could probably be due to interaction of host proteins with RV. b) The host proteins, calreticulin and La (known autoantigens) interact with RV RNA and patients with natural RV infection develop significant anti-La response following prolonged infection. c) Cellular calreticulin chaperones rubella virus E1 glycoprotein and mutations in the E1 glycosylation sites affect viral assembly and release due to perturbations in E1 chaperoning to proper sites of viral assembly. d) Rubella virus non-structural proteins have domains which interact with cell cycle regulatory protein i.e. retinoblastoma protein (RB) both in vivo and in vitro. This interaction could result in the alteration in cell growth upon RV infection and may lead to the RV induced teratogenesis. PROGRESS Recently we have identified a host protein, p32, which the receptor of complement 1 protein's (C1q) "globular head" as rubella virus capsid protein binding protein. This interaction could play a major role in elucidating the transient/chronic arthritis associated with rubella virus vaccine and natural infections.